State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing, 211198, China.
HKUST Shenzhen Research Institute, Shenzhen, 518057, China.
Pharmacol Res. 2019 Nov;149:104459. doi: 10.1016/j.phrs.2019.104459. Epub 2019 Sep 18.
Gut microbiota and their metabolites (short-chain fatty acids, SCFAs) are associated with the pathogenesis of rheumatoid arthritis (RA). Total Clematis triterpenoid saponins (CTSs) prepared from Clematis mandshurica Rupr. possess therapeutic benefits for arthritic diseases. However, the poor pharmacokinetic properties of CTSs have obstructed the translation of these natural agents to drugs. Here, we examined the effects of CTSs on arthritis symptoms, gut microbiota and SCFAs in rats with collagen-induced arthritis (CIA). Our results showed that the arthritis index scores of CIA rats treated with CTSs were significantly lower than those of the model group. Most importantly, CTSs moderated gut microbial dysbiosis and significantly downregulated the total SCFA concentration in CIA rats. Compared to the control group, CTSs treatment have no significant side effects on the gut microbiota and SCFA metabolism in normal rats. Two differential analyses (LEfSe and DESeq2) were combined to study the details of the changes in gut microbiome, and twenty-four marker taxa at the genus level were identified via a comparison among control, model and CIA rats treated with high doses of CTSs. In particular, the mostly significantly increased gram-negative (G) and decreased gram-positive (G) genera in CIA rats were well restored by CTSs. The observed SCFA concentrations demonstrated that CTSs tend to maintain the balance of the gut microbiota. The data presented herein suggest that CTSs could ameliorate arthritis-associated gut microbial dysbiosis and may be potential adjuvant drugs that could provide relief from the gastrointestinal damage caused as a side effect of commonly used drugs.
肠道微生物群及其代谢产物（短链脂肪酸，SCFAs）与类风湿关节炎（RA）的发病机制有关。从Clematis mandshurica Rupr. 中制备的总白头翁三萜皂苷（CTSs）对关节炎疾病具有治疗益处。然而，CTSs 的药代动力学性质差阻碍了这些天然药物向药物的转化。在这里，我们研究了 CTSs 对胶原诱导关节炎（CIA）大鼠关节炎症状、肠道微生物群和 SCFAs 的影响。我们的结果表明，用 CTSs 治疗的 CIA 大鼠的关节炎指数评分明显低于模型组。最重要的是，CTSs 调节肠道微生物群失调，并显著下调 CIA 大鼠的总 SCFA 浓度。与对照组相比，CTSs 治疗对正常大鼠的肠道微生物群和 SCFA 代谢没有明显的副作用。两种差异分析（LEfSe 和 DESeq2）结合起来研究肠道微生物组变化的细节，并通过比较对照、模型和 CIA 大鼠中高剂量 CTSs 治疗的大鼠，鉴定出 24 个属水平的标记分类群。特别是，在 CIA 大鼠中明显增加的革兰氏阴性（G）和减少的革兰氏阳性（G）属通过 CTSs 得到了很好的恢复。观察到的 SCFA 浓度表明 CTSs 倾向于维持肠道微生物群的平衡。本研究结果表明，CTSs 可以改善关节炎相关的肠道微生物群失调，并且可能是潜在的辅助药物，可以缓解常用药物引起的胃肠道损伤。
